A single course of low-dose radiation therapy led to significant reductions in pain and improvements in physical function in mild-to-moderate knee osteoarthritis (OA), a randomized trial from South Korea showed.
At 4 months, a significantly greater number of patients achieved clinically relevant symptomatic improvement with the low-dose course compared with sham treatment (70.3% vs 41.7%, P=0.014), reported Byoung Hyuck Kim, MD, PhD, of Seoul National University College of Medicine.
A very low-dose of radiation showed no significant benefit, but the study provides objective evidence for the efficacy of low-dose radiation therapy as a potential conservative treatment option, Kim said at the American Society for Radiation Oncology (ASTRO) annual meeting here.
OA affects an estimated 32.5 million U.S. adults, with the knee being the joint most commonly involved.
An unmet need in the treatment of knee OA exists between conservative care and invasive surgery, Kim explained. And while low-dose radiation therapy is a non-invasive and non-inflammatory option, the modality has lacked high-quality evidence to support its use, and its optimal dose has been uncertain, according to Kim.
Considering these are short-term results, ASTRO discussant Gopal Bajaj, MD, MBA, of the Inova Schar Cancer Institute in Fairfax, Virginia, observed that the long-term follow-up will help determine whether the response with low-dose radiation therapy is durable.
Kim presented the primary results of a three-arm multicenter trial (LoRD-KNeA) conducted in South Korea, which randomized 114 adults with mild-to-moderate knee OA to a single course of either low-dose radiation (3 Gy), very low-dose radiation (0.3 Gy), or sham radiation (0 Gy) over six fractions.
Eligible adults had to be ages 50 to 85 years and have primary knee OA (Kellgren-Lawrence grade 2-3, baseline walking pain score of 50-90 out of 100 on visual analog scale [VAS]). Use of concomitant analgesics, except for rescue medication, was restricted during the first 4 months, and re-irradiation was not allowed.
The primary endpoint of the trial was response at 4 months on the Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT-OARSI) system, with a positive response defined as either more than 50% improvement in pain and function and at least 20% absolute improvement, or at least 20% improvement in two or more of pain, function, and patient global assessment.
The response rate at 4 months in the very low-dose radiation group was 58.3%.
Secondary endpoints included responses at 1, 8, and 12 months, and Kim noted that 1-month responses were similar among the three groups, at roughly 60% in each.
"It is interesting to note that there is a very heavy placebo response," said Bajaj. "But the groups do separate," he added, noting that the 70% response rate in the low-dose arm "is quite good."
Kim also reported that a clinically meaningful improvement in the Western Ontario and McMaster Universities Arthritis Index score (used to assess pain, stiffness, and function in OA), was observed more frequently in the low-dose radiation group compared with sham (56.8% vs 30.6%, P=0.024).
There were no significant differences in the mean changes from baseline in other secondary outcomes, including VAS, patient global assessment, serum inflammatory markers, and the amount of rescue drug used. No treatment-related toxicity was reported.
"One thing to keep in mind is that the real-world experience that we all have will be clouded by analgesic use," Bajaj pointed out. "Not everyone gets to treat these patients in a controlled environment where we tell patients to stop taking their pain meds."
The results also need to be reproduced in a more diverse population, he added, and said future dose-finding studies could identify an effective dose range between 0.3 and 3 Gy.
Disclosures
The study was supported by funding from Korea Hydro & Nuclear Power.
Kim had no disclosures.
Bajaj reported relationships with Varian Medical Systems, Fuse Oncology, and Totipotent Capital.
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